Pembrolizumab: No Survival Gains Second Line In Gastric Cancer

BARCELONA—Pembrolizumab did not significantly improve overall survival (OS) or progression free survival (PFS) compared with paclitaxel as second-line therapy in patients with advanced gastric or gastro-esophageal junction cancer that had progressed after one line of chemotherapy (containing a platinum and fluoropyrimidine) in the KEYNOTE-061 randomized open-label controlled phase three trial reported at the ESMO 20th World Congress on Gastrointestinal Cancer. https://www.ncbi.nlm.nih.gov/pubmed/29880231.

Molecular Biomarker

The lack of statistical benefit was despite the fact that the analysis was with patientswho had been selected because they had programmed cell death ligand 1 (PD-L1) combined positive scores (CPS) of 1 or higher—indicating at least a one per cent positive staining rate in their tumors—marking them as theoretically ideal candidates for therapy with this checkpoint inhibitor antibody that targets programmed cell death 1 (PD-1) molecular features.

The findings call into question the simplistic concept that targeting a molecular feature on a particular tumor will necessarily be sufficient to work as a method of treating that cancer.

Sub-Groups

But lead author Kohei Shitara MD, Chief Doctor in the gastrointestinal department of the National Cancer Center Hospital East in Kashiwa, Japan, said that sub-group analysis yielded positive findings for some patients and that pembrolizumab had a better safety profile than paclitaxel.

He tells the Audio Journal of Oncology: “The trial did not meet the primary endpoints to show survival improvement [or] PFS improvement,” he said. But some of the patients showed “very durable benefit” with pembrolizumab. The sub-group study confirmed that patients with good performance status and having at least 10 per cent staining for PD-L1 expression (defined as a CPS score of 10) had improved prospects—as did those with tumors expressing high microsatellite instability (MSI).